Postoperative Chemoradiation in Patients With Node-positive Esophageal Squamous Cell Carcinoma

Esophageal Neoplasms Clinical Trial

Official title:

Phase I /II Study of Postoperative Chemoradiation in Patients With Node-positive Esophageal Squamous Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02446574
• Other study ID #: 02-27/230
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 26, 2015
• Last updated: October 20, 2017
• Start date: July 2007
• Est. completion date: December 2016

Study information

• Verified date: October 2017
• Source: Chinese Academy of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a unicentered phase I/II study to explore the dose of paclitaxel and cisplatin with radiation therapy, and to document the adverse events for further clinical trial.

Description:

Although preoperative chemoradiation therapy followed by surgery is the most common approach for patients with resectable esophageal cancer, the considerable number of esophageal cancer patients received operation as the first treatment modality. Accordingly, postoperative treatments have been playing an important role because of the poor survival rates of the patients with pathologically positive lymph nodes who have been treated with resection alone. The investigators have proved the value of prophylactic radiation therapy after radical esophagectomy for esophageal carcinoma with positive lymph node metastases under the conventional 2-dimensional radiotherapy methods in subset analysis of prospective randomized clinical trial. For patients with positive lymph nodes, 5 year survival after surgery alone was 28.4%, median overall survival was 24 months, recurrence occurred 34.6% in mediastinal lymph nodes，13.3% in supraclavicular lymph nodes，10% in abdominal lymph nodes. Distant metastases occurred in 21% patients. Adjuvant radiotherapy significantly reduced the recurrence in mediastinal lymph nodes(13.4%), supraclavicular lymph nodes (6.1%). However distant metastases rate increased to 30.7%. Chemotherapy may be vital for these patients. Chen reported that the 5 year overall survival rates for the chemoradiotherapy group and radiotherapy group were 47.4% and 38.6% (P=0.03). Based on the investigators' studies, treatment failure occurred in 8% patients because of celiac metastases. Small radiation field by omitting celiac axis lymph node basin may ensure 5-6 cycles of concurrent chemotherapy for lower toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 68 Years

Eligibility

Inclusion Criteria:

1. KPS=70

2. Diagnosis of pathologically positive lymph node thoracic esophageal cancer

3. Complete resection

4. Adequate organ function:

Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 150,000/mm^3 Hemoglobin at least 10 g/dL Hepatic Not specified Renal Creatinine no greater than 1.5 mg/dL AND/OR Creatinine clearance at least 65 mL/min Calcium no greater than 11 mg/dL Cardiovascular No uncontrolled heart disease No uncontrolled hypertension

Exclusion Criteria:

1. Uncontrolled diabetes

2. Interval between surgery and adjuvant therapy more than 3 months

3. Sign of recurrence on CT scan or ultrasound or PET-CT No palpable supraclavicular lymph nodes or involvement after cytology needle aspiration No lymph nodes greater than 1 cm on CT scan

4. With Weight loss greater than 10% from baseline

5. With other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix

6. Be pregnant

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Esophageal Neoplasms

Intervention

Drug:
• Paclitaxel
starting dose 20mg/m2 qw
• Cisplatin
dose 25mg/m2 qw

Radiation:
• Radiation
60Gy/2Gy/30f

Locations

Country	Name	City	State
China	Cancer Institute and Hospital, Chinese Academy of Medical Science	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences

Country where clinical trial is conducted

China, 

References & Publications (11)

Chen J, Pan J, Liu J, Li J, Zhu K, Zheng X, Chen M, Chen M, Liao Z. Postoperative radiation therapy with or without concurrent chemotherapy for node-positive thoracic esophageal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):671- — View Citation

Hagen JA, DeMeester SR, Peters JH, Chandrasoma P, DeMeester TR. Curative resection for esophageal adenocarcinoma: analysis of 100 en bloc esophagectomies. Ann Surg. 2001 Oct;234(4):520-30; discussion 530-1. — View Citation

Hsu PK, Huang CS, Wang BY, Wu YC, Hsu WH. Survival benefits of postoperative chemoradiation for lymph node-positive esophageal squamous cell carcinoma. Ann Thorac Surg. 2014 May;97(5):1734-41. doi: 10.1016/j.athoracsur.2013.12.041. Epub 2014 Mar 6. — View Citation

Igaki H, Kato H, Tachimori Y, Nakanishi Y. Prognostic evaluation of patients with clinical T1 and T2 squamous cell carcinomas of the thoracic esophagus after 3-field lymph node dissection. Surgery. 2003 Apr;133(4):368-74. — View Citation

Korst RJ, Rusch VW, Venkatraman E, Bains MS, Burt ME, Downey RJ, Ginsberg RJ. Proposed revision of the staging classification for esophageal cancer. J Thorac Cardiovasc Surg. 1998 Mar;115(3):660-69; discussion 669-70. — View Citation

Liu HC, Hung SK, Huang CJ, Chen CC, Chen MJ, Chang CC, Tai CJ, Tzen CY, Lu LH, Chen YJ. Esophagectomy for locally advanced esophageal cancer, followed by chemoradiotherapy and adjuvant chemotherapy. World J Gastroenterol. 2005 Sep 14;11(34):5367-72. — View Citation

Rice TW, Adelstein DJ, Chidel MA, Rybicki LA, DeCamp MM, Murthy SC, Blackstone EH. Benefit of postoperative adjuvant chemoradiotherapy in locoregionally advanced esophageal carcinoma. J Thorac Cardiovasc Surg. 2003 Nov;126(5):1590-6. — View Citation

Rice TW, Blackstone EH, Rybicki LA, Adelstein DJ, Murthy SC, DeCamp MM, Goldblum JR. Refining esophageal cancer staging. J Thorac Cardiovasc Surg. 2003 May;125(5):1103-13. — View Citation

Rizk N, Venkatraman E, Park B, Flores R, Bains MS, Rusch V; American Joint Committee on Cancer staging system. The prognostic importance of the number of involved lymph nodes in esophageal cancer: implications for revisions of the American Joint Committee — View Citation

van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar — View Citation

Xiao ZF, Yang ZY, Liang J, Miao YJ, Wang M, Yin WB, Gu XZ, Zhang DC, Zhang RG, Wang LJ. Value of radiotherapy after radical surgery for esophageal carcinoma: a report of 495 patients. Ann Thorac Surg. 2003 Feb;75(2):331-6. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of weekly paclitaxel and cisplatin with concurrent radiation(Phase I endpoint)		3 months
Secondary	Toxicities according to the Common Terminology Criteria for Adverse Events version 3.0.		18 months
Secondary	Overall Survival survival of weekly paclitaxel and cisplatin with concurrent radiation(Phase II endpoint)		60 months
Secondary	Disease-free survival of weekly paclitaxel and cisplatin with concurrent radiation(Phase II endpoint)		36 months